The present invention describes processes for preparing 3-alkoxy-2-methylpropenals of the formula ##STR1## wherein R is selected from the group consisting of C.sub.1 -C.sub.10 alkyl, benzyl, 2-propenyl (allyl), and 2-methyl-2-propenyl (methallyl). Preferred "R groups" include: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, allyl, and methallyl. These propenals are also referred to as 3-alkoxymethacroleins and monoenol ether derivatives of methylmalonaldehyde.
Isler, et al have described a procedure wherein 3-ethoxymethacrolein (5), a representative 3-alkoxy-2-methylpropenal, was converted in high yield to 2,7-dimethyl-2,4,6-octatrienedial (a C-10 dialdehyde); see, British patent 866,691 (Apr. 26, 1961). This C-10 dialdehyde is an essential intermediate in the industrial synthesis of many carotenoids, which have found increasing uses in the coloration of foodstuffs and pharmaceuticals and in animal feedstocks. Beta-carotene, a yellow food dye added to oleomargarine among other items, is a representative of this group of naturally occurring compounds, and is illustrated by Formula 1: ##STR2## Other commercially-important carotenoids are canthaxanthin (used commercially as a feed additive and also as a red color additive for food and drugs) and astaxanthin (the red skin pigment of salmon, lobster and trout, and now of increasing importance in the fish-farming industry).
Published syntheses of beta-carotene and related carotenoids have advantageously used the symmetry of the compound to develop convergent synthetic schemes to make the compound. In particular, the ten carbon atom fragment in the center of the compound (the fragment included within the dashed lines as illustrated in Formula 1) has been used in known synthetic schemes. Various methods for preparing this ten carbon atom fragment are described by Isler, Carotenoids, Birkhauser-Verlag, 431-436 (1971).
As noted above, a known preparation of the ten carbon fragment, 2,7-dimethyl-2,4,6-octatrienedial, was developed by O. Isler and his co-workers at Hoffmann-LaRoche. The Roche process, described in O. Isler, et al, Helv. Chim. Acta, 42, 841-853 (1959) and British Patent 866,691, is schematically outlined in Scheme I, and uses 3-ethoxmethacrolein (5) as a key intermediate. This expensive specialty chemical (5) is now available from Aldrich Chemical Co., et al. ##STR3## The bis(diethyl acetal) derivative of dialdehyde 9 has been prepared from intermediate 8 as shown below: ##STR4## This latter bisacetal can be subsequently hydrolyzed using weakly acidic conditions (e.g., acetic acid and water) to obtain dialdehyde 9. See Example XXVI in U.S. Pat. No. 5,107,030 (Apr. 21, 1992) for a similar procedure.
Dialdehyde 9 can be partially hydrogenated as follows: ##STR5## Alternatively, partial hydrogenation of the triple bond in alkyne 9 can be delayed until after the total synthesis of the C-40 carotenoid structure.
The principal disadvantage of the above procedure for forming dialdehyde 10 arises from the cost and method of preparation of the raw materials (2 and 3) required in the first step: 1-ethoxypropene (2) is an expensive, acid-sensitive specialty chemical; and triethyl orthoformate (3) (required in excess) is both costly and requires the toxic chemical chloroform for its manufacture.